Volume 1.08 | May 8

Immunology of Infectious Disease News 1.08 May 8, 2013
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     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs
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TOP STORY
Immune Cells that Suppress Genital Herpes Infections Identified
Scientists have identified a class of immune cells that reside long-term in the genital skin and mucosa and are believed to be responsible for suppressing recurring outbreaks of genital herpes. The discovery of this subtype of immune cells, called CD8αα+ T cells, opens a new avenue of research to develop a vaccine to prevent and treat herpes simplex virus type 2. [Press release from Fred Hutchinson Cancer Research Center discussing online prepublication in Nature] Press Release | Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

The TLR4 Antagonist Eritoran Protects Mice from Lethal Influenza Infection
Investigators report that therapeutic administration of Eritoran (also known as E5564)-a potent, well-tolerated, synthetic Toll-like receptor 4 (TLR4) antagonist-blocks influenza-induced lethality in mice, as well as lung pathology, clinical symptoms, cytokine and oxidized phospholipid expression, and decreases viral titers. [Nature] Abstract | Press Release

T Cells Maintain an Exhausted Phenotype after Antigen Withdrawal and Population Reexpansion
Researchers found that T cells with memory-like properties were generated during chronic infection. After transfer into naive mice, these cells robustly proliferated and controlled a viral infection. [Nat Immunol] Abstract

CD103-CD11b+ Dendritic Cells Regulate the Sensitivity of CD4 T-Cell Responses to Bacterial Flagellin
The authors demonstrated that Toll-like receptor 5 expression by dendritic cells allows a 1,000-fold enhancement of T-cell sensitivity to flagellin, and this enhancement did not require the expression of NLRC4 or Myd88. [Mucosal Immunol] Abstract

Regulation of Rab5 Function in Macrophages during Phagocytosis of Live Pseudomonas aeruginosa
Investigators demonstrated that Rab5 plays a critical role during early stages of P. aeruginosa invasion of J774-Eclone macrophages. They showed that live, but not heat inactivated, P. aeruginosa inhibited phagocytosis, and that this occurred in conjunction with down-regulation of Rab5 activity. [Infect Immun] Abstract

Toll-Like Receptor 4 (TLR4)-Linked Janus Kinase 2 (JAK2) Signaling Contributes to the Internalization of Brucella abortus by Macrophages 
Researchers hypothesized that TLR4-linked signaling interacting with JAK2 plays an essential role in B. abortus phagocytosis by macrophages. The effects of TLR4-JAK2 signaling on B. abortus phagocytosis into murine macrophage RAW264.7 were observed through infection assay and confocal microscopy. [Infect Immun] Abstract

HIV

PD1-Based DNA Vaccine Amplifies HIV-1 GAG-Specific CD8+ T Cells in Mice
Researchers report the development of what they believe to be a novel antigen-targeting DNA vaccine strategy that exploits the binding of programmed death-1 (PD1) to its ligands expressed on dendritic cells by fusing soluble PD1 with HIV-1 GAG p24 antigen. [J Clin Invest] Full Article

Skewing of the CD4+ T Cell Pool Towards Mono-Functional Antigen-Specific Responses in Patients with Immune Reconstitution Inflammatory Syndrome in The Gambia
In a longitudinal cohort study, scientists analyzed 20 patients who developed Immune Reconstitution Inflammatory Syndrome (IRIS) following initiation of anti-retroviral therapy (ART) and 16 patients who did not; matched for ART time-point. PBMC were stimulated overnight with a positive control antigen and two TB-specific antigens (PPD and Esat-6/CFP10) followed by polychromatic flow cytometry for analysis of cytokine production from CD4+ and CD8+ T cells. [Clin Infect Dis] Abstract

Platelet Activation Suppresses HIV-1 Infection of T Cells
The authors found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. [Retrovirology]
Abstract | Full Article

Hierarchy of CD4 T Cell Epitopes of the ANRS Lipo5 Synthetic Vaccine Relies on the Frequencies of Pre-Existing Peptide-Specific T Cells in Healthy Donors
Researchers enumerated Lipo5-specific T cell lines induced in vitro by weekly rounds of specific stimulation. Four peptides and G2 exhibited a broad specificity for HLA-DR molecules. In contrast, most of the T cell lines specific for Lipo5 reacted with G2, revealing a G2-specific T cell repertoire superior to two cells per million, whereas it is close to 0.4 for the other peptides. [J Immunol] Abstract

Interleukin-2 (IL-2) Inhibits HIV-1 Replication in Some HTLV-1-Infected Cell Lines via the Induction and Incorporation of APOBEC3G into the Virion
The authors previously reported that IL-27 inhibits HIV-1 replication in primary T cells in the presence of IL-2. To gain a better understanding of the mechanisms involved in this inhibitory effect, they investigated in detail the effects of IL-27 and IL-2 using several cell lines. [J Biol Chem]
Abstract | Full Article

Genome-Wide Search for the Genes Accountable for the Induced Resistance to HIV-1 Infection in Activated CD4+ T Cells: Apparent Transcriptional Signatures, Co-Expression Networks and Possible Cellular Processes
Scientists showed that following CD3/CD28 co-stimulation, a homogeneous population emerged with uniform expression of activation markers CD25 and CD69 as well as a memory marker CD45RO at high levels. These cells differentially expressed 7,824 genes when compared with the controls on microarrays. [BMC Med Genomics] Abstract

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REVIEWS

Effector and Memory T Cell Responses to Commensal Bacteria
Tissues exposed to commensals have developed elaborate systems of regulation including specialized populations of resident lymphocytes that maintain barrier function and limit potential responses to commensal antigens. However, in settings of infection and inflammation these regulatory mechanisms are compromised and specific effector responses against commensal bacteria can develop. This review discusses the circumstances controlling the fate of commensal specific T cells and how dysregulation of these responses could lead to severe pathological outcomes. [Trends Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the infectious disease research field.

INDUSTRY NEWS

GW School of Medicine and Health Sciences Welcomes Renowned HIV/AIDS Researcher, Douglas F. Nixon, M.D., Ph.D
The George Washington University (GW) School of Medicine and Health Sciences announced that HIV/AIDS researcher, Douglas F. Nixon, M.D., Ph.D., will be joining the faculty on as the Ross Professor of Basic Science Research and chair of the department of microbiology, immunology, and tropical medicine. [George Washington University] Press Release

The Scripps Research Institute Announces New Research and License Agreement with Janssen Pharmaceuticals, Inc.

The Scripps Research Institute announced a five-year agreement with Janssen Pharmaceuticals, Inc. to collaborate on focused research projects in the infectious disease area, with the initial project targeting the influenza virus. [The Scripps Research Institute ] Press Release

Sarepta Therapeutics Initiates Dosing in Phase I Multiple Ascending Dose Study of Drug for Treatment of Marburg Virus

Sarepta Therapeutics, Inc. announced that it has initiated dosing in a Phase I multiple ascending dose (MAD) clinical trial of AVI-7288, the Company’s lead drug candidate for the treatment of Marburg virus infection. The Phase I MAD study is designed to characterize the safety, tolerability and pharmacokinetics of AVI-7288 after repeat dosing in healthy adult volunteers. [Sarepta Therapeutics, Inc.] Press Release

Bristol-Myers Squibb Receives US FDA sNDA Approval for Use of SUSTIVA® (Efavirenz) in HIV-1 Infected Pediatric Patients

Bristol-Myers Squibb Company announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) for SUSTIVA®, including dosing recommendations for HIV-1 infected pediatric patients three months to three years old and weighing at least 3.5 kg. [Bristol-Myers Squibb Company] Press Release

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POLICY NEWS

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

EVENTS

NEW 14th Annual World Vaccine Congress 2013
October 16-17, 2013
Lille, France

NEW SELECTBIO CellTech 2014
January 28-29, 2014
San Diego, United States

Visit our events page to see a complete list of events in the infectious disease community.

JOB OPPORTUNITIES

NEW Postdoctoral Fellow – Stemcell and Cancer Biology (Johns Hopkins University School of Medicine)

Postdoctoral Research Associate – Immunologist (University of Edinburgh)

Postdoctoral Fellow – Host Pathogen Interaction (Columbia Initiative for Systems Biology / Columbia University)


Postdoctoral Position – Immunology and Vaccinology (Université de Liège)

Postdoctoral Position – Immunology (New York University)

Postdoctoral Scientist – Infection by Influenza Virus (National Institute for Medical Research, Medical Research Council)

Assistant Scientist – Immunodeficiency Virus Replication (University of Wisconsin – Madison Primate Research Center)


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